Evaluating outcomes and toxicities for a newly implemented MRI-based brachytherapy program for cervical cancer.

OBJECTIVE: We report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center. METHODS: A retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85-95 Gyα/ß=10 Gy in 2 implants each delivering 2 fractions. RESULTS: Ninety-eight patients were included with median follow up of 24.5 months (IQR 11.9-39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3-118.8) and HR-CTV D90 of 89 Gy (IQR 86.1-90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9-88.0), 65.9 Gy (IQR 59.6-71.2), 65.1 Gy (IQR 57.7-69.6), and 55 Gy (IQR 48.9-60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively. CONCLUSION: MRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease.

Surgery and Platinum/Etoposide-Based Chemotherapy for the Treatment of Epithelioid Trophoblastic Tumor.

OBJECTIVE: Epithelioid trophoblastic tumor (ETT) is a rare variant of gestational trophoblastic neoplasia that develops from chorionic-type intermediate trophoblast, simulates carcinoma, presents years after a pregnancy event, is associated with low or normal human chorionic gonadotropin levels, and is relatively resistant to chemotherapy. Our aim was to identify the role of surgery in combination with platinum/etoposide-based chemotherapy in the management of both localized and metastatic ETT. METHODS: A retrospective review was performed of women with ETT treated at a gestational trophoblastic disease center from 2010 to 2016. RESULTS: Five patients were identified who had complete records. Mean age was 38.0 years. Three women presented with abnormal uterine bleeding, 2 women presented with respiratory complaints, and 1 woman was asymptomatic. Two women had no identifiable antecedent pregnancy, 2 women had spontaneous abortions, and 1 woman had a normal term delivery before diagnosis. Four (80%) of 5 women had metastatic pulmonary disease. All 5 women underwent hysterectomy, and 3 women had resection of metastatic pulmonary disease. The 4 women with metastatic disease were also treated with chemotherapy. All 5 women are currently without evidence of disease. CONCLUSIONS: Surgery, including hysterectomy and resection of metastatic disease, is an important component in the treatment of women with ETT. Adjuvant chemotherapy with a platinum/etoposide-containing regimen should be used in women with metastatic disease. All 5 women with ETT in this series were cured using this approach, including the 4 who had metastatic disease.

Synuclein-γ in uterine serous carcinoma impacts survival: An NRG Oncology/Gynecologic Oncology Group study.

BACKGROUND: Synuclein-γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG-8023). METHODS: High-density tissue microarrays (TMAs) of tumor tissues from 313 patients with USC were stained by immunohistochemistry for SNCG, p53, p16, FOLR1, pERK, pAKT, ER, PR, and HER2/neu. Associations of SNCG and other tumor markers with overall and progression-free survival were assessed using log-rank tests and Cox proportional-hazards models, which also were adjusted for age, race, and stage. RESULTS: The overall survival at 5 years was 46% for women with high SNCG expression and 62% for those with low SNCG expression (log-rank P = .021; hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.91-1.9 in adjusted Cox model). The progression-free survival rate at 5 years was worse for women who had high SNCG expression, at 40%, compared with 56% for those who had low SNCG expression (log-rank P = .0081; HR, 1.36; 95% CI, 0.96-1.92 in adjusted Cox model). High levels of both p53 and p16 were significantly associated with worse overall survival (p53: HR, 4.20 [95% CI, 1.54-11.45]; p16: HR, 1.95 [95% CI, 1.01-3.75]) and progression-free survival (p53: HR, 2.16 [95% CI, 1.09-4.27]; p16: HR, 1.53 [95% CI, 0.87-2.69]) compared with low levels. CONCLUSIONS: This largest collection of USCs to date demonstrates that SNCG was associated with poor survival in univariate analyses. SNCG does not predict survival outcome independent of p53 and p16 in models that jointly consider multiple markers. Cancer 2017;123:1144-1155. © 2016 American Cancer Society.

A pilot study of surgical training using a virtual robotic surgery simulator.

BACKGROUND AND OBJECTIVES: Our objectives were to compare the utility of learning a suturing task on the virtual reality da Vinci Skills Simulator versus the da Vinci Surgical System dry laboratory platform and to assess user satisfaction among novice robotic surgeons. METHODS: Medical trainees were enrolled prospectively; one group trained on the virtual reality simulator, and the other group trained on the da Vinci dry laboratory platform. Trainees received pretesting and post-testing on the dry laboratory platform. Participants then completed an anonymous online user experience and satisfaction survey. RESULTS: We enrolled 20 participants. Mean pretest completion times did not significantly differ between the 2 groups. Training with either platform was associated with a similar decrease in mean time to completion (simulator platform group, 64.9 seconds [P = .04]; dry laboratory platform group, 63.9 seconds [P < .01]). Most participants (58%) preferred the virtual reality platform. The majority found the training "definitely useful" in improving robotic surgical skills (mean, 4.6) and would attend future training sessions (mean, 4.5). CONCLUSION: Training on the virtual reality robotic simulator or the dry laboratory robotic surgery platform resulted in significant improvements in time to completion and economy of motion for novice robotic surgeons. Although there was a perception that both simulators improved performance, there was a preference for the virtual reality simulator. Benefits unique to the simulator platform include autonomy of use, computerized performance feedback, and ease of setup. These features may facilitate more efficient and sophisticated simulation training above that of the conventional dry laboratory platform, without loss of efficacy.

Introduction of a computer-based surgical platform in the surgical care of patients with newly diagnosed uterine cancer: outcomes and impact on approach.

OBJECTIVE: To assess the introduction of computer-based surgery (ie, robotic surgery [RBT]) in the treatment of patients with newly diagnosed uterine cancer. METHODS: We identified all patients who presented to our institution for initial surgical care of newly diagnosed uterine cancer from 5/1/07-12/31/10. Perioperative outcomes of laparotomy cases were compared to those of laparoscopic (LSC) or RBT cases. Complications within 30 days of surgery were graded. RESULTS: Of 752 patients, the planned approach was laparotomy in 103 (14%), LSC in 302 (40%), and RBT in 347 (46%). The rate of laparotomy for any reason (planned or converted) was 39% in 2007 compared to 18% in 2010 (P<0.001). Preoperative characteristics for LSC and RBT cases were similar, except 10% versus 15%, respectively, were morbidly obese (P=0.049). The extent of procedure, total nodal counts, and overall complications were similar between the LSC and RBT cases. The median length of stay was shorter for RBT cases (P<0.001). The median total room and operative times were longer for RBT cases (P<0.001), mainly due to cases in which the surgeon had less than ~40 RBT cases of experience. CONCLUSIONS: Robotics can be efficiently introduced into the surgical care of patients with newly diagnosed uterine cancers. RBT cases require the same operative times as LSC cases after accounting for the 40-case learning curve. Both approaches result in similar excellent patient outcomes and remain reasonable approaches for this disease. The introduction of robotics may lead to further reduction in the rate of laparotomy.

Uterine perforation during brachytherapy for cervical cancer: Complications, outcomes, and best practices for forward treatment planning and management.

PURPOSE: The purpose of the study was to determine the incidence of uterine perforations, review the associated complications, and propose guidelines for management of perforations after brachytherapy. METHODS AND MATERIALS: A retrospective chart review was conducted for all patients with cervical cancer who received single or multiple high-dose-rate brachytherapy implants between April 2006 and May 2017 at a single academic institution. CT and MRI images were retrospectively evaluated to record incidences of uterine perforation of tandem during brachytherapy. Acute and long-term complications during and after treatment were scored using the Common Terminology Criteria for Adverse Events, Version 4.0, of the National Cancer Institute. RESULTS: A total of 123 patients were included in the study. Perforations were observed in 22 patients (17.9%) with 31 (6.4%) of the 482 total implants. Of the different categories of adverse events, only the rate of acute infectious complications among those with perforations (n = 3, 13.6%) versus those without perforations (n = 3, 3.0%) was significant (p = 0.040). Two of the three perforated patients with acute infections had mild urinary tract infections, and all resolved without complications or treatment delays. The remaining one patient had a frank perforation of the anterior uterine wall with a subsequent Grade 3 pyometra infection despite administration of prophylactic antibiotics and 1-week treatment delay. This case was eventually resolved with cervical dilation and evacuation of fluid. Long-term complications were not different between the two arms. CONCLUSIONS: Patients with cervical cancer with uterine perforations may be able to safely proceed with brachytherapy treatment without delay or need for prophylactic antibiotics in the acute setting. Further validating data would be able to assist in establishing a new standard of care and help prevent unnecessary and harmful breaks during treatment.

Life impact of urologic pain syndromes.

In order to explore the personal experience of chronic urologic pain we asked patients to journal in their own words their daily symptoms and the effects of those symptoms on home/family life, working life and social life. Journal responses were independently reviewed by three researchers and major themes summarized following an inductive approach. Three major themes were identified concerning symptoms, personal and interpersonal effects of symptoms and related role limitations. Fatigue emerged as a newly recognized symptom that may benefit from treatment. Role limitations are mediated by potentially modifiable personal and interpersonal effects currently not addressed in urologic pain treatment paradigms.

Salvage treatment in recurrent endometrial cancer of the pelvis and peritoneal cavity.

Regional recurrence of endometrial cancer is a challenging yet potentially curable group of patients without defined standard of care. Our aim is to determine optimal methods of salvage therapy for regionally recurrent endometrial cancer. Twenty-two cases of nodal, pelvic, or peritoneal cavity recurrences of endometrial cancer were identified from a single institution database. Univariable Cox proportional hazards models were used to estimate the risk of a second recurrence or death. Kaplan-Meier plots were used to estimate the probability of progression free survival and overall survival among patients in three cohorts: Multimodality therapy (surgery, chemotherapy, and external beam radiotherapy [EBRT] +/- vaginal brachytherapy), non-surgery (chemotherapy or EBRT, or both), and surgery cohort (surgery +/- chemotherapy OR EBRT). Thirteen recurrences (59%) were regional including the pelvic and paraaortic nodes, while nine recurrences (41%) were abdominal. For the entire cohort, the probability of progression free survival at 2 years was 51% (95% CI, 26% - 72%). The 2-year probability of progression free survival was 62% in the multimodality cohort, 40% in the non-surgery cohort, and 38% in the surgery cohort. The 2-year probability of overall survival was 69% (95% CI, 38% - 86%) across our population. At 40 months of follow up, the only living patients belonged to the multimodality cohort. We found no significant association of a definitive salvage regimen for recurrent endometrial cancer of the pelvis and peritoneal cavity. Aggressive use of multimodality therapy with surgery followed by tumor-directed radiotherapy and chemotherapy offers potentially curative therapy for these patients.

Does adjuvant concurrent or sequential chemotherapy increase the radiation-related toxicity of vaginal brachytherapy for endometrial cancer patients?

PURPOSE: To compare radiation toxicity in endometrial cancer patients treated with adjuvant vaginal brachytherapy (VBT) vs. VBT with concurrent chemotherapy (CCT) or sequential chemotherapy (SCT) METHODS: We retrospectively analyzed 131 patients with endometrial cancer treated with VBT without external beam radiation therapy. Toxicities were graded according to the Common Terminology Criteria for Adverse Events v4.03. CCT was defined as VBT delivered between the first and last cycle of chemotherapy (CT); SCT was defined as VBT delivered before or after CT. RESULTS: Median followup was 36 months, with a 3-year survival rate of 88%. Of the 131 patients, 92 were treated with VBT alone, 34 with VBT and CCT, and 5 with VBT and SCT. The most common toxicity was vaginal stricture, with 30 (22.9%) patients affected. The distribution of toxicities was vaginal 28%, urinary 12%, rectal 11%, and fatigue 5%; none greater than Grade 2. Compared with patients treated with VBT alone, the addition of CT did not increase the chance of vaginal stricture formation (p = 0.84). The difference in system-specific toxicities between treatment modalities was not statistically significant. CONCLUSION: The most common pelvic toxicity from VBT is vaginal stenosis with other toxicities being infrequent and generally Grade 1. The addition of CT in a sequential or concurrent fashion did not increase the rate of pelvic toxicity from VBT alone.

Early outcomes and impact of a hybrid IC/IS applicator for a new MRI-based cervical brachytherapy program.

PURPOSE: The purpose of this study was to report early outcomes and assess the learning curve in a new MRI-based cervical brachytherapy program. METHODS: We accrued 33 patients prospectively, and only patients with ≥3 months' followup (n = 27) were assessed for disease control and toxicity. Eras were defined as first half and second half for the intracavitary (IC)-only era (n = 13 each), and the intracavitary/interstitial (IC/IS) era was separated by difference in applicator availability (n = 7). Dose to 90% of the high-risk clinical target volume (D90 HR-CTV) and minimum dose to the maximally irradiated 2 cubic centimeters (D2cc) to organs at risk were used to assess dosimetry. Statistics were performed with t tests and Kaplan-Meier method. RESULTS: Median followup was 14.7 months. Median treatment duration was 50.5 vs. 57 days for patients treated with external beam radiation therapy at our institution vs. an outside institution (p = 0.03). One-year local control, noncervical pelvic control, distant metastasis-free rate, and overall survival were 84.0%, 96.0%, 78.5%, and 91.3%, respectively. When comparing the first half and second half eras of IC only, there were no differences in median D90 HR-CTV or D2cc of the bladder, rectum, or sigmoid. Comparing the entire IC era to the IC/IS era, median D90 HR-CTV trended higher from 88.0 Gy to 92.9 Gy (p = 0.11). D2cc rectum decreased from 69.3 Gy to 62.6 Gy (p = 0.01), and D2cc bladder trended lower from 87.5 Gy to 83.6 Gy (p = 0.09). CONCLUSIONS: There was no significant difference between the first half and second half eras with IC-only MRI-based brachytherapy. Incorporation of an IC/IS applicator generated the greatest dosimetric improvement. Early results of the MRI-based brachytherapy program are favorable.

Comparison of dosimetric and clinical outcomes between short- and long-channel cylinder applicators for vaginal brachytherapy in intermediate- and high-risk endometrial cancer.

PURPOSE: Vaginal brachytherapy (VBT) using a cylinder applicator is a standard treatment of intermediate- and high-risk endometrial cancer. We conducted a retrospective study of the dosimetric and clinical outcomes at our institution with 2 single-channel applicators in patients receiving VBT. METHODS AND MATERIALS: One hundred thirty-six patients with endometrial cancer treated from 2006 to 2016 receiving VBT after definitive surgery were evaluated. Two cylinders were used with the distal dwell position 7.1-12.8 mm from the apex varying by diameter (short channel), and 3.2 mm from the apex (long channel). We prescribed 18-26 Gy in 3-4 fractions at 0.5 cm depth. Measurements of the distance from the apex to the prescription isodose line were taken from CT imaging. Student's t test and the Wilcoxon rank-sum test were used with corrections for multiple comparisons. RESULTS: Patients had International Federation of Gynecology and Obstetrics 2009 Stage I-II disease (70 Stage IA, 58 Stage IB, 9 Stage II). Mean cylinder apex dose was 95.2% and 154.7% of prescription (p < 0.001), and mean distance from apex to the prescription isodose line was 0.54 mm and 3.5 mm (p < 0.001) for the short- and long-channel cylinders, respectively. There were no significant differences in any toxicity between cylinders. Four patients (2.9%) had vaginal recurrence, all of whom were treated with the short-channel cylinder. Cylinder type was not associated with vaginal recurrence (p = 0.27). CONCLUSIONS: A cylinder applicator with a distal dwell position closer to the apex results in higher doses to the vaginal cuff and increased D2cc to the bladder. All four recurrences were in the short-channel cylinder. Additional investigation into applicator design and impact on patient outcomes in larger cohorts with sufficient followup is warranted.

The effect of estradiol on in vivo tumorigenesis is modulated by the human epidermal growth factor receptor 2/phosphatidylinositol 3-kinase/Akt1 pathway.

To determine whether the epidermal growth factor receptor 2 (ErbB2) and Akt1 can alter the in vivo growth of MCF-7 cells, parental cells or cells stably transfected with constitutively active Akt1 (myr-Akt1) or dominant-negative Akt1 mutants (K179M-Akt1 and R25C-Akt1) were implanted into athymic nude mice. Tumor growth was monitored in the presence or absence of the antiestrogen tamoxifen and the selective ErbB2 inhibitor, AG825. MCF-7 [parental or empty vector transfected, cytomegalovirus (CMV)] and myr-Akt1 cells formed tumors upon estradiol supplementation after 20-30 d (59-, 29-, and 17-fold increase in tumor volume, respectively). Tamoxifen and AG825 blocked the estradiol effect by 93 and 96% in MCF-7 xenografts, 88 and 81% in CMV xenografts, and 91% in myr-Akt1 xenografts. Furthermore, AG825 suppressed the growth of established tumors in CMV and myr-Akt1 inoculated animals by 68 and 75%, respectively, as compared with continued estrogen supplementation, suggesting a role for ErbB2. When K179M-Akt1 or R25C-Akt1 cells were injected into ovariectomized animals, tumor growth was reduced upon estradiol treatment by 95% and 98%, respectively, supporting a role for Akt1. In contrast to ovariectomized animals, in intact animals, myr-Akt1 cells could establish tumors without estradiol priming after 40-50 d (20-fold increase in tumor volume). Loss of Akt1 phosphorylation was associated with tumor growth inhibition. Immunohistochemical assays showed that in tumors from parental and CMV xenografts, estradiol decreased estrogen receptor-alpha expression and induced progesterone receptor expression and Akt phosphorylation, effects that were inhibited by tamoxifen, AG825, and R25C-Akt1 by 89, 82, and 77% for progesterone receptor expression and 48, 66, and 73% for pAkt expression, respectively. Cumulatively, our results suggest that Akt1 and ErbB2 are involved in in vivo tumorigenesis and modulation of estrogen receptor-alpha expression and activity.

The "hook effect" causing a negative pregnancy test in a patient with an advanced molar pregnancy.

•At high hCG levels in molar pregnancies, a "hook effect" can cause an artificially negative value.•Delay in diagnosis of a molar pregnancy due to the "hook effect" can lead to severe complications.•Suspicion of a molar pregnancy should be communicated so a diluted sample is used to quantify hCG.

The allosteric AKT inhibitor, MK2206, decreases tumor growth and invasion in patient derived xenografts of endometrial cancer.

The purpose of this study was to test the effect of MK2206, an allosteric inhibitor of AKT, on the growth and invasion of patient-derived xenografts (PDX) of endometrial cancer. Three PDX lines, USC1 (uterine serous), EEC2 (endometrioid grade 2) and EEC4 (endometrioid grade 3) of endometrial cancer were grafted under the renal capsule of NSG mice. After 2 weeks of tumor growth the mice were treated with vehicle or 120mg/kg MK2206 twice a week for 3 weeks. Growth of all 3 PDX lines of different type and grade was significantly inhibited in response to MK2206 compared with vehicle control. Histological analysis revealed invasion and spread of EEC2 and EEC4 tumors were significantly decreased with MK2206 treatment. Immunohistochemical analysis showed a decrease in Ki67 in EEC2 upon MK2206 treatment, while USC1 and EEC4 tumors did not show differences in Ki67 levels. PR levels were evident in EEC2 which dramatically increased upon MK2206 treatment. In vitro analysis of EEC4 and AN3CA cells showed a dose-dependent decrease in p(Ser473)-AKT and p(Thr308)-AKT with MK2206. Invasion of EEC4 and AN3CA cells also significantly decreased after 36h and 72h of MK2206 treatment. PDX tumors provide an appropriate model for the testing of compounds that incorporates the heterogeneous nature of endometrial cancer. Further studies to determine efficacy of MK2206 alone or in combination with other compounds can also identify predictors of response to these pathway inhibitors.

Effect of estradiol on estrogen receptor-alpha gene expression and activity can be modulated by the ErbB2/PI 3-K/Akt pathway.

Epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and heregulin-beta1 (HRG-beta1), can modulate the expression and activity of the estrogen receptor-alpha (ER-alpha) via the phosphatidylinositol 3-kinase (PI 3-K)/Akt pathway in the ER-alpha-positive breast cancer cell line, MCF-7. Estradiol can also rapidly activate PI 3-K/Akt in these cells (nongenomic effect). The recent study examines whether Akt is involved in the ER-alpha regulation by estradiol (genomic effect). Stable transfection of parental MCF-7 cells with a dominant-negative Akt mutant, as well as the PI 3-K inhibitors wortmannin and LY 294,002, blocked the effect of estradiol on ER-alpha expression and activity by 70-80 and 55-63%, respectively. Stable transfection of MCF-7 cells with a constitutively active Akt mimicked the effect of estradiol. The changes in ER-alpha expression and activity were abrogated in response to estradiol by an arginine to cysteine mutation in the pleckstrin homology (PH) domain of Akt (R25C), suggesting the involvement of this amino acid in the interaction between Akt and ER-alpha. Experiments employing selective ErbB inhibitors demonstrate that the effect of estradiol on ER-alpha expression and activity is mediated by ErbB2 and not by EGFR. Moreover, anchorage-dependent and -independent growth assays, cell cycle and membrane ruffling analyses showed that Akt exerts estrogen-like activity on cell growth and membrane ruffling and that a selective ErbB2 inhibitor, but not anti-ErbB2 antibodies directed to the extracellular domain, can block these effects. In the presence of constitutively active Akt, tamoxifen only partially inhibits cell growth. In contrast, in cells stably transfected with either a dominant-negative Akt or with R25C-Akt, as well as in parental cells in the presence of a selective ErbB2 inhibitor, the effect of estradiol on anchorage-dependent and -independent cell growth was inhibited by 50-75 and 100%, respectively. Dominant-negative Akt inhibited membrane ruffling by 54%; however, R25C-Akt did not have any effect, suggesting that kinase activity plays an important role in this process. Scatchard analysis demonstrated a 67% reduction in estrogen-binding capacity in cells transfected with constitutively active Akt. No change in binding affinity of estradiol to the receptor was observed upon transfection with either Akt mutant. Taken together, our results suggest that estradiol treatment results in binding to membrane ER-alpha and interaction with a heterodimer containing ErbB2, leading to tyrosine phosphorylation. This results in the activation of PI 3-K and Akt. Akt, in turn, may interact with nuclear ER-alpha, altering its expression and activity.

Establishment of human patient-derived endometrial cancer xenografts in NOD scid gamma mice for the study of invasion and metastasis.

OBJECTIVE: Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis. METHODS: Endometrial tumor tissue fragments (1.5 mm × 1.5 mm) from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6-8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers. RESULTS: Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor. CONCLUSION: Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.

Sweet's syndrome: a cutaneous harbinger of ovarian carcinoma.

Sweet's syndrome, or acute febrile neutrophilic dermatosis, is a condition characterized by fever, neutrophilia, erythematous skin lesions, and a dermal infiltrate consisting predominantly of mature neutrophils on histology. Sweet's syndrome is a reactive phenomenon and should be considered a cutaneous marker of systemic disease, including underlying malignancy. We present a case of a 56-year-old woman who presented with vague abdominal symptoms and a tender, erythematous rash on her extremities. Biopsy of her skin lesions revealed Sweet's syndrome. A work-up for malignancy eventually demonstrated a pelvic mass and carcinomatosis, and a diagnosis of advanced-stage papillary serous ovarian carcinoma was subsequently made. In postmenopausal women who present with Sweet's syndrome, a comprehensive evaluation for malignancy is indicated. In women with a known diagnosis of cancer, Sweet's syndrome may manifest in the detection of persistent or recurrent disease.

Epidural analgesia for treatment of a sickle cell crisis during pregnancy.

BACKGROUND: More than 50% of obstetric patients with sickle cell disease will have a pain crisis during pregnancy, and the management of these cases can be challenging. CASE: A 20-year-old African American with sickle cell disease presented at 29 4/7 weeks of gestation with severe, debilitating leg and back pain. Large doses of intravenous narcotics did not result in significant pain relief, so a lumbar epidural was placed. This resulted in complete pain relief within several minutes. The patient's symptoms resolved over several days and after a short course of narcotics she was discharged to home, and the remainder of her pregnancy was uncomplicated. CONCLUSION: Epidural anesthesia should be considered as a potentially effective treatment for a severe sickle cell crisis in obstetric patients.

Laparoendoscopic single-site surgery in gynaecology: A new frontier in minimally invasive surgery.

UNLABELLED: REVIEW OBJECTIVE: To review the recent developments and published literature on laparoendoscopic single-site (LESS) surgery in gynaecology. RECENT FINDINGS: Minimally invasive surgery has become a standard of care for the treatment of many benign and malignant gynaecological conditions. Recent advances in conventional laparoscopy and robotic-assisted surgery have favorably impacted the entire spectrum of gynaecological surgery. With the goal of improving morbidity and cosmesis, continued efforts towards refinement of laparoscopic techniques have lead to minimization of size and number of ports required for these procedures. LESS surgery is a recently proposed surgical term used to describe various techniques that aim at performing laparoscopic surgery through a single, small-skin incision concealed within the umbilicus. In the last 5 years, there has been a surge in the developments in surgical technology and techniques for LESS surgery, which have resulted in a significant increase in utilisation of LESS across many surgical subspecialties. Recently published outcomes data demonstrate feasibility, safety and reproducibility for LESS in gynaecology. The contemporary LESS literature, extent of gynaecological procedures utilising these techniques and limitations of current technology will be reviewed in this manuscript. CONCLUSIONS: LESS surgery represents the newest frontier in minimally invasive surgery. Comparative data and prospective trials are necessary in order to determine the clinical impact of LESS in treatment of gynaecological conditions.